The malaria parasite Plasmodium falciparum degrades host cell hemoglobin as a part of its intermediary metabolism. The cytotoxic free heme liberated during proteolysis of hemoglobin is polymerized into an insoluble crystalline material termed hemozoin. Hemozoin formation is proposed to be mediated by histidine-rich protein 2 (PfHRP2), a 30 kDa protein made up of several HHAHHAADA repeats that has both been found inside P. falciparum's food vacuole (where proteolysis of heme takes place) and is known to bind free heme. The molecular details of how PfHRP2 may aid in heme polymerization remain unknown, however. Recent studies have revealed that PfHRP2 is capable of binding an extraordinary number of heme molecules and it is suggested that upon heme binding, PfHRP2 may form dimers with 3(10)-helical secondary structure. To investigate this PfHRP2-mediated heme polymerization model further, the repeat sequence of PfHRP2 will be synthesized using C(alpha)-methyl substituted amino acids, which should force the peptide into a 3(10)-helical conformation. The structure of this model PfHRP2 peptide will be studied using NMR, IR, and CD spectroscopies and the heme binding properties will then be studied using electronic absorption spectroscopy, resonance Raman, EPR, and stopped-flow spectroscopies. These studies provide an interesting protein target that may lend molecular clues to the mechanism of hemozoin formation and the role of PfHRP2 in this process. These lessons in the pathology of malaria ought to have important implications in the rational design of novel antimalarial drugs.